Potassium Phosphate, Tribasic → Tert-butyl 4-(6-(butylamino)imidazo[1,2-b]pyridazin-3-yl)-2-fluorobenzylcarbamate

HRID 870657노트

반응식

HRID 870657 반응식
Br[C:2]1[N:6]2[N:7]=[C:8]([NH:11][CH2:12][CH2:13][CH2:14][CH3:15])[CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1.[F:16][C:17]1[CH:31]=[C:30](B2OC(C)(C)C(C)(C)O2)[CH:29]=[CH:28][C:18]=1[CH2:19][NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(#N)C.O>[CH2:12]([NH:11][C:8]1[CH:9]=[CH:10][C:5]2[N:6]([C:2]([C:30]3[CH:29]=[CH:28][C:18]([CH2:19][NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:24])[CH3:25])=[C:17]([F:16])[CH:31]=3)=[CH:3][N:4]=2)[N:7]=1)[CH2:13][CH2:14][CH3:15]

참가 물질

6

반응물 3

HCID 62657Potassium Phosphate, TribasicHCID 669802924-(n-Boc-aminomethyl)-3-fluorobenzeneboronic acid pinacol esterHCID 866963223-Bromo-6-(butylamino)imidazo[1,2-b]pyridazine

생성물 1

HCID 86696354Tert-butyl 4-(6-(butylamino)imidazo[1,2-b]pyridazin-3-yl)-2-fluorobenzylcarbamate수율 38%

시약·촉매·용매 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 18373917Acetonitrile--water (1/1)용매

반응 조건

온도
145 °C

실험 절차

To a mixture of 3-bromo-N-butylimidazo[1,2-b]pyridazin-6-amine (187 mg, 0.7 mmol), tert-butyl 2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzylcarbamate (293 mg, 1.2 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (24 mg, 0.034 mmol) and tripotassium phosphate (144 mg, 1.04 mmol) was added 3:1 acetonitrile/water (3 mL). The resulting mixture was heated at 145° C. (microwave) for 800 s. The reaction was then filtered and concentrated. The residue was dissolved in methanol, and then filtered again. The filtration was finally purified by preparative HPLC (neutral) to afford tert-butyl 4-(6-(butylamino)imidazo[1,2-b]pyridazin-3-yl)-2-fluorobenzylcarbamate (110 mg, 38% yield) as a white solid: 1H NMR (CHLOROFORM-d) δ: 8.02 (dd, J=11.9, 1.3 Hz, 1H), 7.78-7.89 (m, 2H), 7.74 (d, J=9.6 Hz, 1H), 7.43 (t, J=8.0 Hz, 1H), 7.28 (s, 2H), 6.52 (d, J=9.6 Hz, 1H), 4.95 (br. s., 1H), 4.31-4.57 (m, 3H), 3.45 (td, J=7.1, 5.6 Hz, 2H), 1.68-1.80 (m, 2H), 1.02 (t, J=7.3 Hz, 3H); LRMS (ESI) m/e 414.3 [(M+H)+, calcd for C22H29FN5O2 414.2].

후처리

  1. filtrationThe reaction was then filtered
  2. concentrationconcentrated
  3. dissolutionThe residue was dissolved in methanol
  4. filtrationfiltered again
  5. filtrationThe filtration
  6. customwas finally purified by preparative HPLC (neutral)

출처 및 근거

ORD 기록
ord-08773336cd8d48a1a9c43f4eb4a3b260
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08969565B2

반응 노트

불러오는 중…